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137 Cards in this Set
- Front
- Back
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Name three drugs that distribute to the lungs:
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alfentanil
sufentanil lidocaine |
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with obese patients, which we do we go by, actual or ideal?
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ideal
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name three factors that affect distribution of a drug:
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cardiac output
regional blood flow tissue volume (binding.) |
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Where does the drug distribute first?
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while perfused organs (vessel rich group.)
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Which organs are included in the vessel rich group?
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liver
kidneys brain heart |
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what is secondary distribution?
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distribution to the vessel poor group
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which organs are included in the vessel poor group?
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muscle
viscera skin fat |
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how long does distribution to the vessel poor group take?
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minutes to hours, until equilibrium is obtained
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what is the pneumonic for pharmacokinetics?
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ADME
absorption, distribution, metabolism, excretion |
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name four characteristics of drugs that affect pharmacokinetics:
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size
lipid solubility ionization plasma protein binding |
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Re: pharmacodynamics, what is intrinsic sensitivity?
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response of the receptor to the drug.
the mechanism that allows the action to occur |
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since different people have different intrinsic sensitivity, what question do we ask of the drug when prescribing it?
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what is the plasma concentration of the drug that will cause a response?
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Describe intrinsic sensitivity with digoxin:
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2 different people can have the same digoxin level. One will be toxic, and one will be therapeutic.
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Name 4 things that affect absorption of a drug:
(both drug and site of absorption.) |
solubility of the drug
site of absorption blood flow to the site of absorption surface area of absorption |
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what advantage does intramuscular have over subcutaneous?
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blood flow is better to the intramuscular area. There is local blood flow.
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how much bioavailability does intravenous route have?
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100%
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describe the predictability of oral absorption:
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oral absorption is highly variable in the G.I. tract
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by which method to drugs pass into the bloodstream with oral route?
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passive diffusion
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describe passive diffusion of drugs:
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drug movement from an area of higher concentration to an area of lower concentration
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describe ionization level of lipid soluble drugs:
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they are not ionized. They are unionized.
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In which direction our drugs traveling when active transport is utilized?
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against eight concentration gradient
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who helps out with active transport?
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transport proteins
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which type of transport is pinocytosis?
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active transport
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name one type of drug that gets absorbed by pinocytosis?
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fat soluble vitamins
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describe facilitated diffusion:
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there is a protein carrier that facilitates the diffusion
it is not active |
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name 4 disadvantages of giving a drug by the oral route:
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irritation of G.I. mucosa
emesis destruction of drug by digestive enzymes irregularities in the absorption |
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name 2 situations where gastric emptying will be delayed:
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diabetes
pregnancy |
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if a drug is acidic, how easily will it get absorbed in an acidic environment ?
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more easily
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if a drug is basic, how easily will it get absorbed in a basic environment?
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more easily
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which form of the drug passes through the cell membrane, ionized or unionized?
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unionized
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what will happen to an acidic drug is it is placed in a basic medium?
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it becomes ionized
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what will happen to a basic drug if it is placed in an acidic medium ?
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it becomes ionized
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chemically, what happens when an acidic drug is placed in a basic medium?
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it donates a proton
it gives up a proton |
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chemically, what happens when an acidic drug is placed in an acidic medium?
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it keeps its electrons
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aspirin is acidic. Describe its chemical state in the stomach :
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mostly unionized
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aspirin is acidic. Describe its chemical state in the small intestine:
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mostly ionized
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Re: travel of drugs, what is steady
state |
concentration of the drug is equal on both sides of the membrane
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which part of the drug is more effective, the ionized part or the unionized part ?
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the unionized part
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when administering drugs rectally, how far in do we give the suppository?
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we want it to pass the internal sphincter
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what will happen regarding absorption if a suppository is absorbed in the lower rectum ?
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it skips first pass metabolism
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when a drug is absorbed rectally, what is the pathway to the liver ?
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it is transported via the portal venous system
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chemically, which types of drugs are up taken by the lung?
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week bases
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how fast is bioavailability with intravenous route?
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rapid
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which type of concoctions prolonged intramuscular absorption ?
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oil or suspension
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chemically, how our drugs absorbed subcutaneous method ?
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simple diffusion
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may we give irritating drugs subcutaneous ?
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no. Only non
irritating drugs |
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what will happen with larger molecules given subcutaneous ?
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they end up going to the circulation by lymphatic channels
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which blood vessel does the drug travel through with first pass ?
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portal vein
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with first pass, we are does the drug stock before entering the bloodstream ?
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liver
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in terms of "who can get in", described the blood brain barrier:
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there is restricted access
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how are endothelial capillaries connected in the blood brain barrier ?
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tight junctions
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what are endothelial capillaries surrounded by with the blood brain barrier ?
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glial tissue
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chemically, what types of drugs cannot get past the blood brain barrier ?
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water
soluble drugs |
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who can get a water
soluble drug across the blood brain barrier ? |
transport protein
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which types of drugs have no problem getting across the blood brain barrier ?
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lipid soluble
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what is the "volume of distribution"
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"vd"
the amount of drug distributed outside the blood and plasma |
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what is the formula for vd ?
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vd = amount of drug and body/C
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name three things that influence vd ?
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degree of binding to plasma proteins
degree of binding to tissue proteins partition coefficient of drug in fat (solubility.) |
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In terms of the anatomy, where is vd taking place ?
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extra vascular tissues
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who has a larger volume of distribution, and why ?
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babies
this is because they are like a big bag of water |
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as an example, if you give 100 mg of a lipid soluble drug, how much will be left in the plasma after absorption from the bloodstream ?
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2 mg
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as an example, if you give 100 mg of a polar drug, how much is left in the plasma after absorption ?
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90 mg
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how permanent is plasma protein binding ?
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it is not permanent. It is reversible
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how much water, comparably, do obese people have in their body ?
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less than us
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what is alpha 1 glycoprotein ?
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some patients have less of it. If you give a basic drug, there will be more free drug. You must give a smaller dose.
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Re: protein binding, what happens with liver disease ?
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reduced binding
there is less plasma proteins there is a higher unbound fraction of the drug the effect of the drug is increased |
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Re: protein binding, what happens with nephrotic syndrome ?
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same as liver disease. There is less plasma proteins, so there is more unbound drug
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what happens when a patient has elevated levels of alpha 1 glycoproteins
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"acute phase reaction response"
there is high levels of alpha 1 glycoproteins this enhances binding |
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which diseases promote increased alpha 1 glycoprotein ?
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cancer
myocardial infarction arthritis |
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what if a patient has liver disease, cancer ?
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they will have low plasma proteins, but they have high alpha 1 glycoproteins. Basic drugs could be more bound, etc.
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give one example with neonates where physio chemical competition and binding occurs
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sulfonamides, competition with bilirubin. This causes bilirubin encephalopathy
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Re: binding of drugs to plasma proteins, how selective is the process ?
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it is a nonselective process
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name 3 tissues where tissue binding can occur
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liver
fat bone but, tissue binding can occur in any tissue |
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if a drug is protein bound, when will it be able to undergo passive diffusion ?
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after it becomes unbound
drugs can find and unbind to plasma proteins |
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what is the purpose of drug metabolism
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to render the drug water
soluble so it can be excreted in the kidneys |
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how high is the vd with water
soluble drugs ? |
small. There is renal excretion
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how high is renal excretion with lipid soluble drugs ?
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small. They are not water
soluble |
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what does it mean if a drug has a high hepatic extraction ratio ?
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the drug is extracted mainly in the liver
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what determines whether a drug with high hepatic extraction ratio gets extracted ?
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it is dependent on blood flow to the liver
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what does it mean if a drug has low hepatic extraction ratio ?
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it's extraction is independent of blood flow
hepatic clearance is dependent on liver enzyme activity |
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describe hepatic drug clearance with congestive heart failure
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decreased clearance secondary to decreased hepatic blood flow
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describe cirrhosis hepatic extraction with cirrhosis
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decreased hepatic blood flow and decreased hepatic enzymes
so, all drugs have trouble being extracted |
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name 15 drugs that have high hepatic extraction ratio
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bupivacaine, diltiazem, fentanyl
ketamine lidocaine meperidine metroprolol morphine Narcan propofol sufentanil verapamil propanolol all of these drugs rely on hepatic blood flow for metabolism |
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name some of drugs that have low hepatic extraction ratio
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Valium
Ativan methadone Dilantin rocuronium theophylline theopental |
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what happens during phase 1 reaction ?
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there is oxidation or reduction
cyp 450 does its work there is hydrolysis, which renders the drug water soluble by introducing a polar group (making the drug ionized.) |
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We're is cyp 450 contained ?
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in the hepatic smooth muscle endoplasmic reticulum (microsomal enzymes.)
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Of the over 1000 cytochrome p450 enzymes, how many are active ?
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50
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from which families come the active CYP iso
enzymes ? |
1, 2, 3
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what percentage of drugs do CYP isoenzymes from families 1, 2, 3 act on ?
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70 to 80%
these are the only ones we are interested in |
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names 25 drugs that undergo metabolism by 3a4
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acetaminophen, alfentanil, Xanax, bupivacaine, cisapride, codeine, Cortisol, Valium, digoxin, diltiazem,fedlopine, fentanyl,granistron, lidocaine, methadone, versed, nicardipine, nifedipine, Prilosec, Printronix, ropivicaine,statins,sufentanil,verapamil, Coumadin
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what happens with phase 2 reaction ?
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there is a formation of covalent linkage. There is a "coupling" of the drug between functional groups which are highly polar. This renders the drug polar and it is excreted through the urine or stool
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name 4 polar functional groups that participate in binding with phase 2 reaction
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glucuronate
sulfate acetate amino acid |
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name 2 genetic factors that affect metabolism
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cytochrome p450
plasma cholinesterase |
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describe phase 1 in phase 2 enzyme throughout the lifespan
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they begin to mature after two to four weeks of life. Newborns metabolize drugs slowly
they mature and the second decade of life after the second decade, function begins to decline |
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name 4 environmental factors (exogenous compounds) that affect drug metabolism
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diet, pollution, smoking, EtOH
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Re: metabolism, described the level of metabolism with smokers and neuromuscular blocking drugs
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they chew through them. There is an induction to metabolism
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what does inhibition of metabolism do to drug concentration ?
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increases it
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what does induction of metabolism do to drug concentration ?
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decreases it
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what happens with first pass affect with induction ?
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there is enhanced first pass affect and reduced bioavailability
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drugs undergo 2 fates after metabolism. What are they ?
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they are either excreted unchanged or converted to metabolites
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name 8 places where drugs are excreted
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kidneys, lungs, skin, bile, intestines, breast milk, saliva, sweat
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what is the formula for "clearance"
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CL = rate of the elimination/C
fraction of dose absorbed X dose dose interval/Css (steady state plasma concentration.) |
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What is the rate of elimination with first order kinetics ?
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it depends on plasma concentration.
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What is the rate of elimination with zero order kinetics ?
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it is linear. It occurs over a period of time
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what is elimination half life
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the time necessary for plasma concentration of the drug to decrease 50% during the elimination phase
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how many half lives are required for almost complete elimination ?
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five
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what determines how often drugs are administered ?
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half
life |
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what if you give a larger dose of a drug? How does this affect half life ?
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half
life is not dose dependent |
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by which order kinetics are the majority of drugs cleared by ?
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first order kinetics
some drugs are cleared by zero order kinetics (like alcohol) |
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what is effect site equilibration ?
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the delay between the drug administration and the clinical effect
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name some intravenous drugs that have short effect site equilibration
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short
(remifentanil, alfentanil, propofol.) rapid onset, go away quickly |
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name some intravenous drugs that have long effect site equilibration ?
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fentanyl
sufentanil versed |
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what is bioavailability in terms of first pass metabolism
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it is the fraction of drug which is absorbed and escapes first pass metabolism
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what are the 2 components to pharmacodynamic mechanism of action ?
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interaction with macromolecular components of the organisms
drug/receptor interaction |
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name 3 G. protein receptors
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opioid, histamine, musacrinic/cholinergic
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name 4 ligand gated ion channel
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serotonin
GABA glycine acetylcholine receptor channel |
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give one example where drugs cause an effect by stimulating/inhibiting enzyme systems
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phosphodiesterase inhibitors
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what effect does an agonist have on the target when it interacts with a receptor ?
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stimulation
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what effect does an antagonists have on a target when it interacts with a receptor ?
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it interferes with the agonist. The result is no pharmacological effect
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what causes down regulation ?
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continued stimulation with an agonist
is associated with tachyphylaxis |
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what is happening with up regulation ?
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there is chronic interference with receptor activity
there is exaggerated response. |
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How is pharmacological effect measured with drugs ?
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ED 50
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what is ED 50 ?
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the dose required to produce an effect in 50% of subjects
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describe ceiling effect
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the effect plateaus. If you give more, you do not get anymore affect. You just make the patient more toxic
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name 2 drugs that need high receptor occupancy to have an effect
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neuromuscular blockers
inhaled anesthesia |
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in the dose response curve, which drug is more potent, the one on the left or the one on the right ?
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the one on the left. There is more "effect" with a lower dose of that drug
(example: morphine has more pain relief than Demerol, so it will be on the left.) |
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What is the formula for therapeutic index ?
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TI = LD/ED
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Re: therapeutic index, what is safest ?
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wide therapeutic index.
(example: heparin and digoxin have a narrow therapeutic index.) |
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Describe additive effect
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1 + 1 = 2
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describe synergistic effect
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1+1 >2
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give one example of time synergism
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adding epinephrine to a local anesthetic to prolong the effect
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describe competitive antagonism with neuromuscular blockers
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the drug sits on the receptor, so you need more acetylcholine to compete
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describe noncompetitive antagonism with ketamine
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the drug produces a conformational change on the receptor. It gets onto the NMDA receptor site
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what is cross tolerance ?
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tolerance to a drug with a similar profile
example: alcohol and benzodiazepines |
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what is tachyphylaxis ?
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an acute tolerance to pharmacological effect.
example: Nipride |
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what is drug dependence ?
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psychological or physical need to have the drug
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what is happening with drug interactions ?
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1 drug alters the profile of the other drug
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